Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37)
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Data
2013-05-16
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Universidade Federal de Goiás
Resumo
Melanoma is a type of cancer that arises from melanocytes and is notoriously resistant to
radiation and chemotherapy. The thiosemicarbazones are synthetic compounds with marked
biological properties such as antibacterial, antiviral, antiprotozoal and antitumor and previous
studies have demonstrated cytotoxic activity against the human melanoma cells, so in this
study, we evaluated the antiproliferative activity, the enzymatic activity of Caspases 2, 3, 6, 8,
9, the effect on the cell cycle gene expression levels of caspases 2, 3, 6, 8, 9, Apaf-1 and
microscopic morphological changes in human melanoma cells (SK -MEL-37) twenty one
monoterpene derived from natural thiosemicarbazone (-) - camphene: camphene,
benzaldehyde, benzophenone, menthone, ethyl pyruvate, p-nitroacetophenone, pchloroacetophenone,
p-methoxyacetophenone, p-methylacetophenone, p fluoracetofenona-phidroxiacetofena,
furan, 3-methoxy-4-hydroxybenzaldehyde, p-fluorbenzaldehyde, 2-
hydroxybenzaldehyde, cinnamic aldehyde, thiophene-2-carboxaldehyde, 1-H-imidazole-4-
carboxaldehyde, tiossemicaroazida and six montoterpeno natural R-(+)-limonene:
benzaldehyde, thiosemicarbazide, o-nitro, m-nitro, p-nitro, p-hydroxy and p-dimethylamino.
The values found for the inhibitory concentration for 50% of cells (IC50) were between 12
μM and 55 μM. The percentage of cells in phase and in phase G0/G1 decreased SG2 / M
increased after forty-eight hours of incubation with benzaldehyde thio-camphene, limonene
thio-benzaldehyde, m-nitro, p-hydroxy and thiosemicarbazide increased indicating that the
growth inhibitory effect might be also due to arrest of cells at S-G2/M phase. We observed
increased activity of caspase 3 (m-nitro thio-limonene), 6 (camphene thio-benzaldehyde and
p-hydroxy thio-limonene) and 8 (thio-benzaldehyde limonene). Late apoptotic features were
detected in 62% of cells treated with benzaldehyde thio-camphene and morphological changes
typical of apoptosis were visualized by fluorescence microscopy and scanning electron
microscopy (SEM) after treatment with benzaldehyde thio-camphene chosen due to their low
IC50 value (12 mM). It was observed gene expression of caspases 2, 3, 6, 8 and Apaf-1 in
cells treated with benzaldehyde thio-camphene indicating the participation of these enzymes
in the anti-proliferative effect observed. Our results indicate that the thiosemicarbazones
derivatives can inhibit proliferation, regulate cell cycle, induce apoptosis of human melanoma
cells (SK-MEL-37) and could be an candidate for future preclinical in vivo studies.
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PASSOS, Débora Cristina Silva dos. Ação biológica in vitro de tiossemicarbazonas derivadas de canfeno e limoneno em células de melanoma humano (SK-MEL-37). 2013. 84 f. Tese (Doutorado em Biologia) - Universidade Federal de Goiás, Goiânia, 2013.